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    Summary
    EudraCT Number:2015-001377-40
    Sponsor's Protocol Code Number:MO29694
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-08-16
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2015-001377-40
    A.3Full title of the trial
    PHASE II, EXPLORATORY, MULTICENTER, NON RANDOMIZED, SINGLE AGENT COHORT STUDY TO DETERMINE BEST TUMOR RESPONSE WITH TRASTUZUMAB EMTANSINE IN HER2 OVEREXPRESSING SOLID TUMORS.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Determine Best Tumor Response With Trastuzumab Emtansine in HER2 Overexpressing Solid Tumors.
    A.3.2Name or abbreviated title of the trial where available
    KAMELEON
    A.4.1Sponsor's protocol code numberMO29694
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. Hoffmann-La Roche Ltd
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name KADCYLA®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTRASTUZUMAB EMTANSINE
    D.3.9.1CAS number 1018448-65-1
    D.3.9.2Current sponsor codeRO5304020
    D.3.9.3Other descriptive nameT-DM1, Trastuzumab-MCC-DM1
    D.3.9.4EV Substance CodeSUB35467
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeAntibody-drug conjugate comprised of a humanized monoclonal antibody (trastuzumab) and emtansine (DM1).
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Human epidermal growth factor receptor 2 (HER2) overexpressing solid tumors specifically metastatic urothelial bladder cancer (MUBC) as well as pancreas/cholangio cancer, which are locally advanced or have spread to other tissues and organs.
    E.1.1.1Medical condition in easily understood language
    Solid tumors are masses of abnormal tissue growth that originate in organs or soft tissues and do not include fluid areas and cysts. HER2 is a protein that can affect the growth of some cancer cells.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10033575
    E.1.2Term Pancreas cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10046721
    E.1.2Term Urothelial carcinoma bladder stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10005003
    E.1.2Term Bladder cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10008594
    E.1.2Term Cholangiocarcinoma non-resectable
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of trastuzumab emtansine by best overall response rate (BOR) as determined by the investigator (using response evaluation criteria in solid tumors [RECIST] 1.1).
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of trastuzumab emtansine by progression free survival (PFS) as determined by the investigator (using RECIST 1.1) and overall survival (OS)
    • To evaluate the safety of trastuzumab emtansine
    • To evaluate the immune response to trastuzumab emtansine
    • To identify biomarkers that are predictive of response, can provide evidence of trastuzumab emtansine activity, or can increase the knowledge and understanding of disease biology.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Histologically centrally confirmed HER2-positive (Immunohistochemistry [IHC] 3+ in >= 30% of tumor cells): locally advanced, metastatic or unresectable (not treatable with curative intent) urothelial bladder cancer (UBC) or pancreas/cholangio cancer
    - There must be no standard treatment options available for patients with the above HER2 overexpressing tumors and they must have undergone at least one prior platinum-based treatment for inoperable, locally advanced or metastatic tumor (Note: for pancreas/cholangio cancer, prior treatments are NOT required to be platinum-based.)
    - The patient must have evaluable disease fulfilling all of the following imaging criteria:
    • On diagnostic computed tomography (CT) scan/ magnetic resonance imaging (MRI): lesion should be measurable according to RECIST 1.1
    • Target lesion(s) should not have been previously irradiated
    - At least one formalin-fixed paraffin-embedded biopsy of the primary tumor and/or from a metastatic site is required
    - Age >= 18 years
    - Eastern cooperative oncology group (ECOG) performance status of 0-1
    - No significant cardiac history and a current left ventricular ejection fraction (LVEF) >= 50%. LVEF should be determined within 28 days before the start of trastuzumab emtansine treatment
    - Adequate organ function
    - Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
    - Negative serum pregnancy test for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (12 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy
    - For women of childbearing potential and men with partners of childbearing potential, agreement by the patient and/or partner to use a highly effective non-hormonal form of contraception such as surgical sterilization or two effective forms of non-hormonal contraception until 7 months after the last dose of trastuzumab emtansine
    - Life expectancy of at least 12 weeks.
    E.4Principal exclusion criteria
    - Patients with previous exposure to HER2-targeted therapies in any setting
    - Patients showing histologically confirmed focal HER2-expression, i.e., < 30% of positively stained tumor cells
    - Patients with bone only metastases are not eligible
    - Patients with brain metastasis as the sole site of metastatic disease and are symptomatic or require therapy to control symptoms
    NB: Brain metastases are allowed provided they are asymptomatic and/or controlled by previous radiotherapy.
    - Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic 100 mmHg)
    - Current unstable angina pectoris
    - History of symptomatic congestive heart failure (CHF) of any New York Heart Association criteria or ventricular arrhythmia that requires treatment
    - History of myocardial infarction within the last 6 months
    - Peripheral neuropathy, Grade >= 3
    - Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
    - Current severe, uncontrolled systemic disease
    - History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned
    - For female patients, current pregnancy and lactation
    - Concurrent, serious, uncontrolled infections or current known infection with human immunodeficiency virus, active hepatitis B and/or hepatitis C
    - Known prior severe hypersensitivity to trastuzumab and trastuzumab emtansine or the excipients of the investigational medicinal product
    - Clinically significant bleeding within 30 days before enrollment
    - Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
    - Concurrent participation in any other therapeutic clinical trial.
    E.5 End points
    E.5.1Primary end point(s)
    1. BOR (Best overall response rate) as determined by the investigator (using RECIST 1.1). BOR is defined as the best response recorded from the first day of study treatment until disease progression/recurrence or death.
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. The total length of the study for an individual cohort, from screening of the first patient to the end of the study, is expected to be approximately 3 years (18 months of recruitment, 6 months of treatment and 12 months of follow-up).
    E.5.2Secondary end point(s)
    1) PFS (Progression-free survival), defined as the time from beginning of treatment to the first occurrence of disease progression, as determined by the investigator (using RECIST 1.1), or death from any cause, whichever occurs first
    2) OS (Overall survival), defined as the time from beginning of treatment to death from any cause
    3) Incidence, type and severity of all adverse events (AEs) and serious adverse events
    4) Incidence and type of AEs leading to discontinuation, modification, or delay of trastuzumab emtansine dose
    5) Changes in vital signs, physical examination findings, and clinical laboratory results
    6) Number of deaths and its causes
    7) Cases of drug-induced liver injury meeting Hy’s Law criteria
    8) Pneumonitis of all grades
    9) Change in LVEF over the course of the study as measured by echocardiogram or multiple-gated acquisition scan
    10) Incidence of CHF
    11) Incidence of anti-therapeutic antibodies (ATAs) during the study relative to the prevalence of ATAs at baseline
    12) Exploratory assessment of immune checkpoint-inhibitors and infiltrating lymphocytes in the tumor before and after treatment by the assessment of immune-related biomarkers such as programmed T-cell death ligand-1 (PDL1) and cluster of differentiation 8 (CD8)
    13) To evaluate the HER2 status by immunohistochemistry (IHC) and in situ hybridization (ISH)
    14) Correlate levels of HER2 protein expression, HER2 gene amplification and circulating HER2 extracellular domain (HER2 ECD) to trastuzumab emtansine efficacy
    15) Evaluate biomarkers that may be associated with response and/or safety on the protein, ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) level.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-15. The total length of the study for an individual cohort, from screening of the first patient to the end of the study, is expected to be approximately 3 years (18 months of recruitment, 6 months of treatment and 12 months of follow-up).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 56
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state23
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 76
    F.4.2.2In the whole clinical trial 76
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Currently, the Sponsor does not have any plans to provide trastuzumab emtansine or any other study treatments or interventions to patients who have completed the study. The study will be concluded after the last patient has been followed up for 18 months after last patient has been enrolled. Patients who have not progressed at the end of the trial and who are still on treatment will be offered the possibility to continue treatment in an extension study.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-08-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-11-21
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-04-09
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